DESCRIPTION: In this Phase I project, Dr. Draheim proposes to develop methods of hemopurification using sorptive techniques. Substances to be removed are drugs, drug metabolites, and related compounds which will pass through membranes so that there will not be direct contact between the sorbent and blood of the patient. The approach will minimize removal of substances from blood which are normal components and required for normal metabolism. Among the goals are treatment of drug overdosage, some forms of renal and hepatic insufficiency, and also metabolites of drugs which are used in chemotherapy, but may be harmful to cells and tissues as they circulate at toxic levels. Dr. Draheim states that the technique will not deplete platelets, induce hemolysis, or introduce any of the sorbent material as microemboli into the patient's circulation. The technique will employ blood plasma, which has a long shelf life. In depicting the system, one observes that toxic material will pass from the patient's circulation through hollow fiber membranes in the module into a circulating pool of normal plasma. The material will then enter a bed of sorbent particles which will act upon it. Normal pooled human plasma will be equilibrated with the sorbents and with highly permeable hydrophobic membranes so that relatively non-dialyzable possibly toxic materials can be removed. The pre-equilibration step with plasma will avoid losing desirable substances from the patient's circulation. Attention is also given to excessive citrate passing into the patient through the membrane. Desirable substances are not removed because there is a separate circuit of plasma equilibrated with sorbent. Also, fine particles of sorbent cannot enter the patient's circulation. Dr. Draheim has had experience will filtration procedures for whole human blood using hollow porous fibers for obtaining plasma. The sorbents to be used are powdered active carbon and granular active carbon. Resins may also be tried. A wide variety of membrane materials will be tested. This will include polypropylene, various types of celluloses and acrylics. Cost and permeability properties will be taken into consideration. Experimental systems will be designed according to current techniques for extracorporeal therapy for terminal renal disease. For Phase I, experiments will not be carried out with animal or human volunteers. During Phase I, the FDA will be asked about how to extend the work if successful into the animal and human domain. As the system is designed commercially, the plasma can be stored therein for up to 5 years. Lyophilized plasma may also be used, in which case sterile saline will be added to reconstitute the system. Safety precautions are already in place for another Phase II project. Pre-screened blood for HIV and hepatitis will be purchased from the Red Cross. Donor anonymity will be assured.